The objectives of the current proposal are to characterize the in vitro culture system by which specifically sensitized lymphocytes are generated by cocultivation with murine mammary tumor cells, to utilize it to ascertain the basic mechanisms underlying the in vivo immune responses to mammary tumors, and to determine optimal conditions for obtaining successful therapeutic effects when lymphocytes sensitized in vitro are transferred into tumor bearing mice. In the initial studies, the optimal conditions for in vitro generation of cytotoxic effector activity against syngeneic mammary tumor cells were determined. The cytotoxic effector activity obtained under these conditions was mediated by T-cells and specific against mammary tumor cells of the same H-2 haplotype, although less though significant cross-reactivity was observed against allogeneic mammary tumor cells. In the coming year, studies will be performed to investigate the immunotherapeutic effects of the immune effector cells by determining the fate of these cells after transfer into tumor bearing mice.